A systematic review of spirostanol saponins and anticancer natural products isolated from Tacca plantaginea (Hance) Drenth.

The plant genus Tacca comprises twenty species including Tacca plantaginea, essentially distributed in the Indo-China region. Medicinal preparations from the rhizomes are used traditionally to treat gastrointestinal ailments, stomach aches and inflammatory disorders. A variety of bioactive molecules have been isolated from T. plantaginea, including potent anticancer steroids such as the taccanolides which interfere with microtubules dynamic. Other efficient anticancer natural products have been isolated from the plant, in particular a series of diosgenin/yamogenin-type sapogenins including taccaoside (monodesmosidic) and taccaoside A (bidesmosidic). Taccaoside A displays marked anticancer properties through two complementary mechanisms: a direct action on cancer stem cells via HRas and Pi3K/Akt signaling and an indirect immunomodulatory action via activation of cytotoxic T cells. A similar mechanism of action has been invoked with a total saponin extract from Schizocapsa plantaginea Hance (synonym to T. plantaginea) and the saponin SSPH 1. This saponin reduced tumor growth in mice through stimulation of cytotoxic T lymphocytes. Other bioactive products have been isolated from T. plantaginea, including withanolide-type steroids (plantagiolides, chantriolides), diarylheptanoids (plantagineosides) and different saponins (diosbulbisides, lieguonins). The discussion centers around the mechanism of action of spirostanol saponins, with the objective to promote their study as immuno-active anticancer agents.

Innocuité d'une recette médicinale traditionnelle utilisée pour l'infertilité masculine en Côte d'Ivoire / Safety of a traditional medicinal recipe used for male infertility in Ivory Coast

L'infertilité masculine est incriminée dans 50% des cas d'infertilité du couple. C'estun réel problème de santé publique en Afrique.Le présent travail avaitpour objectif d'évaluer l'innocuité et la tolérabilitéd'une recette médicinaletraditionnelle utilisée pour la prise en charge del'infertilité masculine dans le District Autonome d'Abidjan/Côte d'Ivoire. Cette étude a été réalisée dans le cadre de la valorisation de la pharmacopée africaine.Le matériel végétal était constitué de la recette médicinale et le matériel biologiquede 42 volontaires de sexe masculinsélectionnés sur une base raisonnée à postériori.Les volontaires ont été soumis à un traitement sur troismois. Lesvariables étudiées étaient: la glycémie,l'urée, la créatinine, les transaminases, les triglycérides et le cholestérol total. Leseffets secondaireset indésirablesont été notifiés.L'âge moyen de la populationd'étudeétait de 41,78 ans (± 7,73). Aux termes des trois mois d'utilisation de la recette médicinale, l'analyse statistiquedes variables biochimiquesa révélé: la glycémiep = 0,12; les transaminases p = 0,75; la créatinine p = 0,26; l'urée p = 0,04; les triglycérides p =0,95et le cholestérol total p = 0,64contre p< 0,05.Le principal effet secondaire notifié était la polyurie (97,5%).Ces résultatsaffirmentla sécurité de la recette médicinalepourl'utilisateur. Ils encouragentson utilisation chez les hommes infertileset un suivimédicaldespersonnes sous antihypertenseur.La recette médicinale présente une bonne innocuité et une bonne tolérabilité

Male infertility is incriminated in 50% of cases of couple infertility. This is a real public health problem in Africa.The present work aimed to evaluate the safety and tolerability of a traditional medicinal recipe used to treatmale infertilitMale infertility is incriminated in 50% of cases of couple infertility. This is a real public health problem in Africa.The present work aimed aimed to the safety and tMale infertility is incriminated in 50% of cases of couple infertility. This is a real public health problem in Africa.The present work aimed to evaluate the safety and tolerability of a traditional medicinal recipe used to treatmale infertility in the Autonomous District of Abidjan/Côte d'Ivoire. This study was carried out as part of the promotion of the African pharmacopoeia.The plant material consisted of the medicinal recipe and the biological material of 42 male volunteers selected purposively asposteriori. The volunteers underwent treatment over three months. The variables studied wereblood sugar, urea, creatinine, transaminases, triglycerides and total cholesterol. Side effects and undesirable effects were reported.The average age of the study population was 41.78 years (± 7.73). After three months of use of the medicinal recipe, the statistical analysis ofbiochemical variables revealedblood sugar p = 0.12; transaminases p = 0.75; creatinine p = 0.26; urea p = 0.04; triglycerides p = 0.95 and total cholesterol p = 0.64 versus p < 0.05. The main side effect reported was polyuria (97.5%).These results affirm the safety of the medicinal recipe for the user. They encourage its use in infertile men and medical monitoring of people on antihypertensive medication.The medicinal recipe isgood safety and tolerability.

Genomic, spatial and morphometric data for discrimination of four species in the Mediterranean Tamus clade of yams (Dioscorea, Dioscoreaceae).

BACKGROUND AND AIMS: Among the numerous pantropical species of the yam genus, Dioscorea, only a small group occurs in the Mediterranean basin, including two narrow Pyrenean endemics (Borderea clade) and two Mediterranean-wide species (D. communis and D. orientalis, Tamus clade). However, several currently unrecognized species and infraspecific taxa have been described in the Tamus clade due to significant morphological variation associated with D. communis. Our overarching aim was to investigate taxon delimitation in the Tamus clade using an integrative approach combining phylogenomic, spatial and morphological data. METHODS: We analysed 76 herbarium samples using Hyb-Seq genomic capture to sequence 260 low-copy nuclear genes and plastomes, together with morphometric and environmental modelling approaches. KEY RESULTS: Phylogenomic reconstructions confirmed that the two previously accepted species of the Tamus clade, D. communis and D. orientalis, are monophyletic and form sister clades. Three subclades showing distinctive geographic patterns were identified within D. communis. These subclades were also identifiable from morphometric and climatic data, and introgression patterns were inferred between subclades in the eastern part of the distribution of D. communis. CONCLUSIONS: We propose a taxonomy that maintains D. orientalis, endemic to the eastern Mediterranean region, and splits D. communis sensu lato into three species: D. edulis, endemic to Macaronesia (Canary Islands and Madeira); D. cretica, endemic to the eastern Mediterranean region; and D. communis sensu stricto, widespread across western and central Europe. Introgression inferred between D. communis s.s. and D. cretica is likely to be explained by their relatively recent speciation at the end of the Miocene, disjunct isolation in eastern and western Mediterranean glacial refugia and a subsequent westward recolonization of D. communis s.s. Our study shows that the use of integrated genomic, spatial and morphological approaches allows a more robust definition of species boundaries and the identification of species that previous systematic studies failed to uncover.

Chantriolides F-P, Highly Oxidized Withanolides with Hepatoprotective Activity from Tacca chantrieri.

Eleven highly oxidized withanolides, chantriolides F-P (1-11), together with six known analogues (12-17), were isolated from the rhizomes of Tacca chantrieri. Their structures were established on the basis of comprehensive spectroscopic data analysis and comparison with published NMR data, and their absolute configurations were further confirmed by experimental ECD data and single crystal X-ray diffraction analysis. The structures of compounds 5-8 contained a chlorine atom substituted at C-3. Compounds 1 and 12 are a pair of epimers isomerized at C-24 and C-25, while compounds 9 and 16 are isomerized at C-1, C-7, C-24, and C-25. Next, the hepatoprotective effect of all the isolates was evaluated on tert-butyl hydroperoxide (t-BHP)-injured AML12 hepatocytes. Compounds 5-11 and 16 significantly enhanced cell viability. Compound 8 decreased reactive oxygen species accumulation and increased glutathione level in t-BHP injured AML12 hepatocytes through promoting nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2).

In Silico and In Vitro Analysis of Tacca Tubers (Tacca leontopetaloides) from Banyak Island, Aceh Singkil Regency, Indonesia, as Antihypercholesterolemia Agents.

Tacca leontopetaloides (T. leontopetaloides) contain a number of active compounds such as flavonoids, tannins, phenolics, steroids, and alkaloids. The active compounds from plants have been shown to reduce the risk of cardiovascular disease by lowering cholesterol levels by inhibiting the enzyme 3-hydroxy-3-methylglutaryl-coenzym A (HMG-CoA) reductase activity. This study aims to investigate the potential active compounds in the ethanolic extract of Tacca tubers (T. leontopetaloides) from the Banyak Islands, Aceh Singkil Regency, Aceh Province both in vitro and in silico. Tacca tubers contain secondary metabolites including flavonoids, phenolics, tannins, steroids and saponins, according to phytochemical screening. In vitro investigation of ethanolic extract of Tacca tuber revealed inhibitory activity of HMG Co-A reductase with an IC50 value of 4.92 ppm. Based on the in silico study, active compound from the extract, namely Stigmasterol with the highest binding affinities with HMG Co-A reductase (-7.2 kcal/mol). As a comparison, the inhibition of HMG Co-A reductase activity by simvastatin with an IC50 4.62 ppm and binding affinity -8.0 Kcal/mol. Our findings suggest that the ethanolic extract of Tacca tuber (T. leontopetaloides) from Banyak Islands, Aceh Province has the potential to inhibit the activity of HMG Co-A reductase.

Acaricidal Activities of Dioscorea japonica Thunb. (Dioscoreales: Dioscoreaceae) Extract and its Constituents Against the Two-spotted Spider Mite, Tetranychus urticae Koch (Trombidiformes: Tetranychidae).

The acaricidal activities of 86 plant extracts were investigated under laboratory conditions. The ethanol extract of Dioscorea japonica Thunb. root showed the strongest acaricidal activity, with 89.3% mortality against two-spotted spider mite, Tetranychus urticae Koch adults at a 2 mg/ml concentration. Bioassay-guided isolation of D. japonica root extract using silica gel open column chromatography, gas chromatography (GC), and gas chromatography-mass spectrometry (GC-MS) identified palmitic acid as the primary active compound. The acaricidal activities of palmitic acid against T. urticae were 91.2% and 69.7% at concentrations of 1 and 0.5 mg/ml, respectively. Among nine saturated fatty acids with carbon chains ranging from C8 to C26, the most vigorous acaricidal activity was observed with octanoic acid, followed by palmitic acid, and decanoic acid at a 1 mg/ml concentration. The acaricidal activity of the other fatty acids was less than 40% mortality at a 1 mg/ml concentration. These results indicate that a suitable carbon length is essential for fatty acids to exhibit acaricidal activity. The acaricidal efficacy of Eungjinssag (EJSG), an organic agricultural material authorized for the management of mites in the Republic of Korea, was compared to D. japonica root extract. At concentrations above 1 mg/ml, the acaricidal activity of D. japonica root extract was stronger than that of EJSG. The results of this study show that D. japonica root extract and palmitic acid are promising candidates as new environmentally-friendly control agents against two-spotted spider mite, which is one of the most severely damaging agricultural arthropod pests.

Taccachatrones A-G, Highly Oxidized Steroids from the Rhizomes of Tacca chantrierii and Their Cytotoxicity Assessment.

Seven highly oxidized steroids, taccachatrones A-G (1-7), together with four known taccalonolides (8-11), were characterized from the rhizomes of Tacca chantrieri. The structures of 1-7 were established on the basis of spectroscopic data analysis, while the absolute configurations were determined by single-crystal X-ray diffraction. Compounds 1-4 may be derived from taccalonolide derivatives by the degradation of three carbon atoms. Compounds 7, 8, 10, and 11 exhibited cytotoxicity to human cancer cell lines, indicating that the presence of a lactone moiety, as well as a double bond between C-22 and C-23, might play key roles in mediating their cytotoxicity.

Taccalonolide Microtubule Stabilizers.

Microtubule stabilizers are a mainstay in the treatment of many solid cancers and continue to find utility in combination therapy with molecularly targeted anticancer agents and immunotherapeutics. However, innate and acquired resistance to microtubule stabilizers can limit their clinical efficacy. The taccalonolides are a unique class of microtubule stabilizers isolated from plants of Tacca that circumvent clinically relevant mechanisms of drug resistance. Although initial reports suggested that the microtubule-stabilizing activity of the taccalonolides was independent of direct tubulin binding, additional studies have identified that potent C-22, C-23 epoxidized taccalonolides covalently bind the Aspartate 226 residue of ß-tubulin and that this interaction is critical for their microtubule-stabilizing activity. The taccalonolides have distinct properties as compared to other microtubule stabilizers with regard to their biochemical effects on tubulin structure and dynamics that promote distinct cellular phenotypes. Some taccalonolides have demonstrated in vivo antitumor efficacy in drug-resistant tumor models with exquisite potency and long-lasting antitumor efficacy as a result of their irreversible target engagement. The recent identification of a site on the taccalonolide scaffold that is amenable to modification has provided evidence of the specificity of the taccalonolide-tubulin interaction. This also affords an opportunity to further optimize the targeted delivery of the taccalonolides to further improve their anticancer efficacy and potential for clinical development.

Neuroprotective and Anti-inflammatory Ditetrahydrofuran-Containing Diarylheptanoids from Tacca chantrieri.

Three new dimeric diarylheptanoids, taccachanfurans A-C (1-3), a new monomeric diarylheptanoid, taccachannoid A (4), and four known diarylheptanoids (5-8) were isolated from the EtOH extract of the rhizomes of Tacca chantrieri. Their structures were established on the basis of comprehensive spectroscopic data analysis. The absolute configuration of taccachanfuran A (1) was confirmed by single-crystal X-ray diffraction. All the diarylheptanoid dimers contain a ditetrahydrofuran moiety, which has not been described previously for diarylheptanoid compounds. A plausible biosynthetic pathway for the diarylheptanoid dimers is proposed. Compounds 2-4 showed significant neuroprotective activity against Aß25-35-induced damage in SH-SY5Y cells at the concentrations of 10 and 1 µM. Compounds 3, 4, 6, 7, and 8 showed anti-inflammatory activity in LPS-stimulated murine microglial BV-2 cells at the concentrations of 10 and 1 µM.

High-throughput serum metabolomics analysis of gouty arthritis rat treated by total saponins of Rhizoma Dioscoreae Makino by UPLC-Q/TOF-MS.

Rhizoma Dioscoreae Makino (RDM) is effective in treating gouty arthritis (GA) and hyperuricacidemia, especially in promoting uric acid excretion and reducing the inflammatory reaction. Bioactive constituents in RDM are mainly steroidal saponins such as dioscin, trillin, protodioscin and protogracillin. However, the mechanism of its anti-GA action is still unclear, owing to the complex pathological and physiological characteristics of GA, and integration of RDM with multiple components, multiple targets and multiple pathways. Herein, a GA rat model was induced with monosodium urate (MSU), and RDM reduced inflammation of rat synovium tissue. Through metabolomics analysis, 35 potential biomarkers with significant changes involved in the pathogenesis of GA induced by MSU were identified, and perturbations were restored after RDM treatment. The most correlated pathways involved in d-galactose, d-mannose, d-glucose, myoinositol, Phosphatidylcholine (PC) (16:0/16:0), LysoPC (15:0), phosphatidic acid (PA) [18:1(9Z)/18:1(11Z)] and glutathione induced by MSU were galactose metabolism, inositol phosphate metabolism, glycerophospholipid metabolism and glutathione metabolism, and the derivations of all those biomarkers could be regulated by RDM treatment. RDM has a therapeutic effect on GA by intervening in changes in endogenous metabolisms and the related metabolic pathways.